清华大学刘强团队报道了具有最小不同烷基的氯胺酮的不对称氢化反应。相关研究成果于2024年5月28日发表于国际顶尖学术期刊《自然》。

不对称催化可以合成光学活性化合物，通常需要区分前手性底物上的两个取代基。尽管主要的贵金属催化剂已经发展了几十年，但在具有相似空间和电子性质的取代基之间实现区分仍然是一个重大挑战。

该文中，研究人员介绍了一类用于二烷基酮亚胺不对称氢化的地球丰富的锰催化剂，以产生一系列手性胺产物。这些催化剂区分与酮亚胺结合的最小分化的烷基对，如甲基和乙基，甚至区分更细微的区别，如乙基和正丙基。通过对手性锰催化剂的组分进行改性，可以调节对映选择性的程度。该反应显示出宽的底物范围并实现高达107800的周转数（TON）。

机理研究表明，特殊的立体选择性源于受限手性催化剂的模块化组装，以及催化剂和底物之间的协同非共价相互作用。

附：英文原文

Title: Asymmetric hydrogenation of ketimines with minimally different alkyl groups

Author: Wang, Mingyang, Liu, Shihan, Liu, Hao, Wang, Yujie, Lan, Yu, Liu, Qiang

Issue&Volume: 2024-05-28

Abstract: Asymmetric catalysis allows the synthesis of optically active compounds, often requiring the differentiation between two substituents on prochiral substrates1. Despite decades of development of mainly noble metal catalysts, achieving differentiation between substituents with similar steric and electronic properties remains a significant challenge2,3. Here, we introduce a class of earth-abundant manganese catalysts for the asymmetric hydrogenation of dialkyl ketimines to give a range of chiral amine products. These catalysts distinguish between pairs of minimally differentiated alkyl groups bound to the ketimine, such as methyl and ethyl, and even subtler distinctions, like ethyl and n-propyl. The degree of enantioselectivity can be adjusted by modifying the components of the chiral manganese catalyst. This reaction demonstrates a wide substrate scope and achieves a turnover number (TON) of up to 107,800. Our mechanistic studies indicate that the exceptional stereoselectivity arises from the modular assembly of confined chiral catalysts and cooperative non-covalent interactions between the catalyst and the substrate.

DOI: 10.1038/s41586-024-07581-z

Source: https://www.nature.com/articles/s41586-024-07581-z